Port wine stains (PWS) are congenital, progressive vascular malformations of the skin that occur in approximately 0.7% of neonates and have potentially devastating psychological complications and, in some cases, serious physical effects as well. Current therapies achieve complete blanching of less than 10% of these lesions and multiple treatments (5 -30 or more) are generally required. We intend to combine photodynamic (PDT) and pulsed dye laser (PDL) therapies (PDT + PDL) to achieve permanent destruction of the most clinically relevant PWS blood vessels without injury to the surrounding skin. We will use a vascular specific photosensitizer, benzoporphyrin derivitive monoacid ring A (BPD), and continuous wave (CW) yellow light to confine PDT effects to the most superficial 1.0 mm below the skin surface. Vascular flow will be monitored during PDT using optical Doppler tomography (ODT). CW irradiation will be stopped when a reduction in blood flow is noted or after a light dose of 100 J/cm2 has been delivered. This approach will limit the depth and extent of vascular injury to the targeted vessels and prevent skin necrosis, which would result from total vascular destruction. PDT will be followed immediately, or after a brief time interval, by PDL irradiation to complete superficial vessel destruction without injury to the surrounding skin. Initial experiments using a chick chorioallantoic membrane confirmed the superior efficacy of PDT + PDL PWS vessel destruction as compared to either modality alone. This proposal includes a protocol to confirm the superior efficacy of PDT + PDL using a rat dorsal skin flap window model. The threshold of vascular lesion damage for PDT using BPD and yellow light and optimal treatment parameters for PDT + PDL vascular therapy will also be evaluated using the same animal model. Finally, we will determine the efficacy and safety of PDT + PDL PWS therapy in comprehensive clinical trials. The results of the studies in this proposal are expected to lead to the development of novel and innovative technology which will provide a more effective and, most importantly, safer method for removal of PWS birthmarks.